The protective role of T cell subsets in corneal herpes simplex virus type 1 (HSV-1) infection has been studied. However, the relative contribution of, and the role played by, each particular T cell subset still remain a controversial issue.We studied sequentially the appearance of major histocompatibility (MHC) and viral antigens in HSV-1 infected corneas of Balb/C mice and related them to induction of T cell subsets in local lymph nodes and corneal lesions. Immunohistochemical study has revealed a marked increase of expression of class II MHC antigen in the corneal stromal cells, while class I MHC antigen gradually increased in the corneal epithelium and stroma. Further immunohistochemical survey has revealed that L3T4, antigen bearing and Lyt 2 antigen bearing cells were induced to a similar extent with an equal rapidity in the local lymph nodes as well as in the corneal stroma. Transfer of these subpopulations to syngeneic nude mice showed that they played a role to prevent severe outcome of corneal herpetic infection.These results indicate that the corneal stroma is a major site of the host's immunological activities and both L3T4, and Lyt 2 bearing cells are equally important for the prevention of corneal herpetic infection.